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United States Patent |
6,140,528
|
Hawkins
|
October 31, 2000
|
Intermediates to herbicidal isoxazole and 2-cyano-1,3-dione compounds
Abstract
The invention relates to intermediates to herbicidal compounds of formulae
(Ia), (Ib) or (Ic):
##STR1##
Inventors:
|
Hawkins; David William (Ongar, GB)
|
Assignee:
|
Rhone-Poulenc Agriculture Ltd (Ongar, GB)
|
Appl. No.:
|
444461 |
Filed:
|
November 22, 1999 |
Foreign Application Priority Data
Current U.S. Class: |
558/415; 558/416; 560/18; 562/432; 562/824 |
Intern'l Class: |
C07C 255/49; C07C 255/57; C07C 323/09 |
Field of Search: |
558/415,416
560/18
562/432,825
|
References Cited
U.S. Patent Documents
3073861 | Jan., 1963 | Raasch | 560/18.
|
3102903 | Sep., 1963 | Coffman et al. | 562/824.
|
3117158 | Jan., 1964 | Sheppard, I | 560/18.
|
3219690 | Nov., 1965 | Sheppard, II | 560/18.
|
5656573 | Aug., 1997 | Roberts et al. | 504/271.
|
5849928 | Dec., 1998 | Hawkins, I | 548/248.
|
6013805 | Jan., 2000 | Hawkins, II | 548/248.
|
Foreign Patent Documents |
0213892 | Mar., 1987 | EP.
| |
0418175 | Mar., 1991 | EP.
| |
0487357 | May., 1992 | EP.
| |
0496630 | Jul., 1992 | EP.
| |
0496631 | Jul., 1992 | EP.
| |
0524018 | Jan., 1993 | EP.
| |
0527036 | Feb., 1993 | EP.
| |
0527037 | Feb., 1993 | EP.
| |
0560482 | Sep., 1993 | EP.
| |
0560483 | Sep., 1993 | EP.
| |
0625505 | Nov., 1994 | EP.
| |
0625508 | Nov., 1994 | EP.
| |
2276379 | Sep., 1994 | GB.
| |
2276380 | Sep., 1994 | GB.
| |
2276381 | Sep., 1994 | GB.
| |
2276382 | Sep., 1994 | GB.
| |
95/25099 | Sep., 1995 | WO.
| |
97/05106 | Feb., 1997 | WO.
| |
Other References
Sheppard, J. Am. Chem. Soc., 84, pp. 3064-3072 (1962).
|
Primary Examiner: Higel; Floyd D.
Attorney, Agent or Firm: Burns, Doane, Swecker & Mathis, L.L.P.
Parent Case Text
This application is a divisional of U.S. patent application Ser. No.
09/162,062, filed Sep. 29, 1998, now U.S. Pat. No. 6,013,805, which is a
divisional of U.S. patent application Ser. No. 08/822,926, filed Mar. 21,
1997, now U.S. Pat. No. 5,849,928, both of which are incorporated by
reference herein in their entireties and relied upon.
Claims
What is claimed is:
1. A compound having the formula:
##STR29##
wherein: R.sup.2 is:
halogen;
straight- or branched-chain alkyl having up to six carbon atoms which is
substituted by one or more --OR.sup.5 ;
cycloalkyl having from three to six carbon atoms; or
a member selected from the group consisting of nitro, cyano, --CO.sub.2
R.sup.5, --NR.sup.5 R.sup.6, --S(O).sub.p R.sup.7, --O(CH.sub.2).sub.m
OR.sup.5, --COR.sup.5, --N(R.sup.8)SO.sub.2 R.sup.7, --OR.sup.7, --OH,
OSO.sub.2 R.sup.7, --(CR.sup.9 R.sup.10).sub.t SO.sub.q R.sup.7a,
--CONR.sup.5 R.sup.6, --N(R.sup.8)--C(Z).dbd.Y, --(CR.sup.9
R.sup.10)NR.sup.8 R.sup.11 and R.sup.4 ;
n is zero or an integer from one to three;
when n is greater than one, then the groups R.sup.2 are the same or
different;
m is one, two or three;
p is zero, one or two;
q is zero, one or two;
t is an integer from one to four;
R.sup.4 is straight- or branched-chain alkyl, alkenyl or alkynyl having up
to six carbon atoms which is unsubstituted or is substituted by one or
more halogen;
R.sup.5 and R.sup.6, which are the same or different, are each hydrogen or
R.sup.4 ;
R.sup.7 and R.sup.7a independently are R.sup.4, cycloalkyl having from
three to six ring carbon atoms, or --(CH.sub.2).sub.w -phenyl wherein
phenyl is unsubstituted or is substituted by from one to five R.sup.12
which are the same or different;
w is zero or one;
R.sup.8 is:
hydrogen;
straight- or branched-chain alkyl, alkenyl or alkynyl having up to ten
carbon atoms which is unsubstituted or is substituted by one or more
halogen;
cycloalkyl having from three to six ring carbon atoms;
(CH.sub.2).sub.w -phenyl wherein phenyl is unsubstituted or is substituted
by from one to five R.sup.12 which are the same or different; or
--OR.sup.13 ;
R.sup.9 and R.sup.10 independently are hydrogen or straight- or
branched-chain alkyl having up to six carbon atoms which is unsubstituted
or is substituted by one or more halogen;
R.sup.11 is --S(O).sub.q R.sup.7 or --C(Z).dbd.Y;
R.sup.12 is:
halogen;
straight- or branched-chain alkyl having up to three carbon atoms which is
unsubstituted or is substituted by one or more halogen; or
a member selected from the group consisting of nitro, cyano, --S(O).sub.q
R.sup.3 and --OR.sup.5 ;
Y is oxygen or sulphur;
Z is R.sup.4, --NR.sup.8 R.sup.13, --NR.sup.8 --NR.sup.13 R.sup.14,
--SR.sup.7 or --OR.sup.7 ;
R.sup.13 and R.sup.14 independently are R.sup.8 ;
R.sup.3 is:
straight- or branched-chain alkyl having up to six carbon atoms which is
unsubstituted or
which is substituted by one or more substituents selected from the group
consisting of halogen, --OR.sup.5, --CO.sub.2 R.sup.5, --S(O).sub.p
R.sup.7, phenyl and cyano; or
phenyl which is unsubstituted or which is substituted by one or more
substituents selected from the group consisting of halogen, --OR.sup.5 and
R.sup.4 ; and
R.sub.15 is lower alkyl.
2. A compound according to claim 1, wherein the 2-position of the phenyl
group is substituted.
3. A compound according to claim 1, wherein the 5- and 6-positions of the
phenyl group are unsubstituted.
4. A compound according to claim 1, wherein R.sup.2 is:
halogen;
straight- or branched-chain alkyl or alkenyl having up to four carbon atoms
which is unsubstituted or is substituted by one or more halogen;
or a member selected from the group consisting of nitro, cyano,
--S(O).sub.p R.sup.7, --OR.sup.7 and --CR.sup.9 R.sup.10 SO.sub.q R.sup.7.
5. A compound according to claim 1, wherein n is zero, one or two.
6. A compound according to claim 1, having at least one substituent
selected from the group consisting of:
R.sup.2 is halogen or straight- or branched-chain alkyl having up to three
carbon atoms which is unsubstituted or is substituted by one or more
halogen, or R.sup.2 is --S(O).sub.p R.sup.7 or --CH.sub.2 S(O).sub.q
R.sup.7a ;
R.sup.7 is methyl or ethyl which is unsubstituted or is substituted by one
or more halogen; and
R.sup.7a is straight- or branched-chain alkyl having up to four carbon
atoms which is unsubstituted or is substituted by one or more halogen, or
R.sup.7a is phenyl which is unsubstituted or is substituted by one or more
halogen or --S(O).sub.p R.sup.7.
7. A compound having the formula:
##STR30##
wherein: R.sup.2 is:
halogen;
straight- or branched-chain alkyl having up to six carbon atoms which is
substituted by one or more --OR.sup.5 ;
cycloalkyl having from three to six carbon atoms; or
a member selected from the group consisting of nitro, cyano, --CO.sub.2
R.sup.5, --NR.sup.5 R.sup.6, --S(O).sub.p R.sup.7, --O(CH.sub.2).sub.m
OR.sup.5, --COR.sup.5, --N(R.sup.8 )SO.sub.2 R.sup.7, --OR.sup.7, OH,
--OSO.sub.2 R.sup.7, --(CR.sup.9 R.sup.10).sub.t SO.sub.q R.sup.7a,
--CONR.sup.5 R.sup.6, --N(R.sup.8)--C(Z).dbd.Y, --(CR.sup.9
R.sup.10)NR.sup.8 R.sup.11 and R.sup.4 ;
n is zero or an integer from one to three;
when n is greater than one, then the groups R.sup.2 are the same or
different;
m is one, two or three;
p is zero, one or two;
q is zero, one or two;
t is an integer from one to four;
R.sup.4 is straight- or branched-chain alkyl, alkenyl or alkynyl having up
to six carbon atoms which is unsubstituted or is substituted by one or
more halogen;
R.sup.5 and R.sup.6, which are the same or different, are each hydrogen or
R.sup.4 ;
R.sup.7 and R.sup.7a independently are R.sup.4, cycloalkyl having from
three to six ring carbon atoms, or --(CH.sub.2).sub.w -phenyl wherein
phenyl is unsubstituted or is substituted by from one to five R.sup.12
which are the same or different;
w is zero or one;
R.sup.8 is:
hydrogen;
straight- or branched-chain alkyl, alkenyl or alkynyl having up to ten
carbon atoms which is unsubstituted or is substituted by one or more
halogen;
cycloalkyl having from three to six ring carbon atoms;
--(CH.sub.2).sub.w -phenyl wherein phenyl is unsubstituted or is
substituted by from one to five R.sup.12 which are the same or different;
or
--OR.sup.13 ;
R.sup.9 and R.sup.10 independently are hydrogen or straight- or
branched-chain alkyl having up to six carbon atoms which is unsubstituted
or is substituted by one or more halogen;
R.sup.11 is --S(O).sub.q R.sup.7 or --C(Z).dbd.Y;
R.sup.12 is:
halogen;
straight- or branched-chain alkyl having up to three carbon atoms which is
unsubstituted or is substituted by one or more halogen; or
a member selected from the group consisting of nitro, cyano, --S(O).sub.p
R.sup.3 and --OR.sup.5 ;
Y is oxygen or sulphur;
Z is R.sup.4, --NR.sup.8 R.sup.13, --NR.sup.8 --NR.sup.13 R.sup.14,
--SR.sup.7 or --OR.sup.7 ;
R.sup.13 and R.sup.14 independently are R.sup.8 ;
R.sup.3 is:
straight- or branched-chain alkyl having up to six carbon atoms which is
unsubstituted or which is substituted by one or more substituents selected
from the group consisting of halogen, --OR.sup.5, --CO.sub.2 R.sup.5,
--S(O).sub.p R.sup.7, phenyl and cyano; or
phenyl which is unsubstituted or which is substituted by one or more
substituents selected from the group consisting of halogen, --OR.sup.5 and
R.sup.4 ;
with the proviso that when n is zero, then the --SF.sub.5 group is not meta
or para to the carboxy group.
8. A compound according to claim 7, wherein the 2-position of the phenyl
group is substituted.
9. A compound according to claim 7, wherein the 5- and 6-positions of the
phenyl group are unsubstituted.
10. A compound according to claim 7, wherein R.sup.2 is:
halogen;
straight- or branched-chain alkyl or alkenyl having up to four carbon atoms
which is unsubstituted or is substituted by one or more halogen;
or a member selected from the group consisting of nitro, cyano,
--S(O).sub.p R.sup.7, --OR.sup.7 and --CR.sup.9 R.sup.10 SO.sub.q R.sup.7.
11. A compound according to claim 7, wherein n is zero, one or two.
12. A compound according to claim 7, having at least one substituent
selected from the group, consisting of:
R.sup.2 is halogen or straight- or branched-chain alkyl having up to three
carbon atoms which is unsubstituted or is substituted by one or more
halogen, or R.sup.2 is --S(O).sub.p R.sup.7 or --CH.sub.2 S(O).sub.q
R.sup.7a ;
R.sup.7 is methyl or ethyl which is unsubstituted or is substituted by one
or more halogen; and
R.sup.7a is straight- or branched-chain alkyl having up to four carbon
atoms which is unsubstituted or is substituted by one or more halogen, or
R.sup.7a is phenyl which is unsubstituted or is substituted by one or more
halogen or --S(O).sub.p R.sup.7.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to novel isoxazole derivatives and 2-cyano-1,3-dione
derivatives, compositions containing them, processes for their
preparation, intermediates in their preparation and their use as
herbicides.
2. Description of the Background Art
Herbicidal 4-benzoylisoxazoles are described in European Patent Publication
Numbers 0418175, 0487357, 0527036, 0527037, 0560482 and 0560483.
Herbicidal 2-cyano-1,3-diones are described in European Patent Publication
Numbers 0213892, 0496630, 0496631, 0625505 and 0625508, and International
Patent Publication No. WO 95/25099. Herbicidal 5-phenylisoxazoles are
described in European Patent Publication Number 0524018. However, none of
the above publications disclose or suggest the presence of a
pentafluorosulphanyl group as a substituent on the phenyl ring.
SUMMARY OF THE INVENTION
The present invention provides 4-benzoylisoxazole derivatives of formula
(Ia), 5-phenylisoxazole derivatives of formula (Ib) and 2-cyano-1,3-dione
derivatives of formula (Ic):
##STR2##
wherein:
R represents hydrogen or --CO.sub.2 R.sup.3 ;
R.sup.1 represents:
a straight- or branched-chain alkyl group containing up to six carbon atoms
which is optionally substituted by one or more halogen atoms; or
a cycloalkyl group containing from three to six ring carbon atoms
optionally substituted by one or more groups selected from R.sup.4 and
halogen;
R.sup.2 represents:
halogen;
a straight- or branched-chain alkyl group containing up to six carbon atoms
which is substituted by one or more groups --OR.sup.5 ;
a cycloalkyl group containing from three to six carbon atoms; or a group
selected from nitro, cyano, --CO.sub.2 RS, --NR.sup.5 R.sup.6,
--S(O).sub.p R.sup.7, --O(CH.sub.2).sub.m OR.sup.5, --COR.sup.5,
--N(R.sup.8)SO.sub.2 R.sup.7, --OR.sup.7, --OH, --OSO.sub.2 R.sup.7,
--(CR.sup.9 R.sup.10).sub.t SO.sub.q R.sup.7a, --CONR.sup.5 R.sup.6
--N(R.sup.8)--C(Z).dbd.Y, --(CR.sup.9 R.sup.10) )NR.sup.8 R.sup.11 and
R.sup.4 ;
n represents zero or an integer from one to three; where n is greater than
one the groups R.sup.2 may be the same or different;
m represents one, two or three;
p represents zero, one or two;
q represents zero, one or two;
t represents an integer from one to four (preferably one);
R.sup.3 represents a straight- or branched-chain alkyl group containing up
to six carbon atoms optionally substituted by one or more groups selected
from halogen, --OR.sup.5, --CO.sub.2 R.sup.5, --S(O).sub.p R.sup.7, phenyl
or cyano; or phenyl optionally substituted by one or more groups selected
from halogen, --OR.sup.5 and R.sup.4 ;
R.sup.4 represents a straight- or branched-chain alkyl, alkenyl or alkynyl
group containing up to six carbon atoms optionally substituted by one or
more halogen atoms;
R.sup.5 and R.sup.6 which may be the same or different, each represents
hydrogen or R.sup.4 ;
R.sup.7 and R.sup.7a independently represent R.sup.4 or a cycloalkyl group
containing from three to six ring carbon atoms; or a group
--(CH.sub.2).sub.w --[phenyl optionally substituted by from one to five
groups R.sup.12 which may be the same or different];
w represents zero or one;
R.sup.8 represents: hydrogen;
a straight- or branched-chain alkyl, alkenyl or alkynyl group containing up
to ten carbon atoms optionally substituted by one or more halogen atoms;
a cycloalkyl group containing from three to six ring carbon atoms;
--(CH.sub.2).sub.w --[phenyl optionally substituted by from one to five
groups R.sup.12 which may be the same or different]; or
a group --OR.sup.13 ;
R.sup.9 and R.sup.10 independently represent hydrogen or a straight- or
branched-chain alkyl group containing up to six (preferably up to three)
carbon atoms optionally substituted by one or more halogen atoms;
R.sup.11 represents --S(O).sub.q R.sup.7 or --C(Z).dbd.Y;
R.sup.12 represents: a halogen atom;
a straight- or branched-chain alkyl group containing up to three carbon
atoms optionally substituted by one or more halogen atoms;
or a group selected from nitro, cyano, --S(O).sub.p R.sup.3 and --OR.sup.5
;
Y represents oxygen or sulphur (preferably Y represents oxygen);
Z represents R.sup.4, --NR.sup.8 R.sup.13, --NR.sup.8 --NR.sup.13 R.sup.14,
--SR.sup.7 or --OR.sup.7 ;
R.sup.13 and R.sup.14 independently represent R.sup.8 ;
and agriculturally acceptable salts and metal complexes thereof, which
possess valuable herbicidal properties.
Compounds of formula (Ic) may exist in enolic tautomeric forms that may
give rise to geometric isomers around the enolic double bond. It will also
be appreciated that certain substituents in the compounds of the invention
may contribute to optical isomerism and/or stereoisomerism. All such forms
are embraced by the present invention.
DETAILED DESCRIPTION OF THE INVENTION AND PREFERRED EMBODIMENTS
It will be understood that in the description that follows, reference to
compounds of formula (I) means reference to compounds of formula (Ia),
(Ib) or (Ic).
By the term "pentafluorosulphanyl" is meant a radical of the formula
--SF.sub.5, which can also be termed "pentafluorothio".
By the term "agriculturally acceptable salts" is meant salts the cations or
anions of which are known and accepted in the art for the formation of
salts for agricultural or horticultural use. Preferably the salts are
water-soluble. Suitable salts with bases include alkali metal (eg. sodium
and potassium), alkaline earth metal (eg. calcium and magnesium), ammonium
and amine (eg. diethanolamine, triethanolamine, octylamine, morpholine and
dioctylmethylamine) salts. Suitable acid addition salts, formed by
compounds of formula (I) containing an amino group, include salts with
inorganic acids, for example hydrochlorides, sulphates, phosphates and
nitrates and salts with organic acids, for example acetic acid.
By the term "metal complexes" is meant compounds in which one or both of
the oxygen atoms of the 1,3-dione of formula (Ic) act as chelating agents
to a metal cation. Examples of such cations include zinc, manganese,
cupric, cuprous, ferric, ferrous, titanium and aluminium.
Compounds of formula (Ia) are preferred.
Compounds in which the 2-position of the phenyl group is substituted are
also preferred.
Preferably the 5- and 6-positions of the phenyl group are unsubstituted.
Preferably R.sup.1 represents:
a straight- or branched-chain alkyl group containing up to three carbon
atoms which is optionally substituted by one or more halogen atoms; or
cyclopropyl or 1-methylcyclopropyl.
Most preferably R.sup.1 represents cyclopropyl.
Preferably R.sup.2 represents:
halogen;
a straight- or branched-chain alkyl or alkenyl group containing up to four
carbon atoms optionally substituted by one or more halogen atoms;
or a group selected from nitro, cyano, --S(O).sub.p R.sup.7, --OR.sup.7 and
--CR.sup.9 R.sup.10 SO.sub.q R.sup.7.
Preferably n represents zero, one or two.
Preferably R.sup.3 represents a straight- or branched-chain alkyl group
containing up to six carbon atoms optionally substituted by one or more
halogen atoms.
Preferably R.sup.7 represents a straight- or branched-chain alkyl group
containing up to six carbon atoms which is optionally substituted by one
or more halogen atoms;
or phenyl optionally substituted by halogen, a straight- or branched-chain
alkyl containing up to three carbon atoms optionally substituted by one or
more halogen atoms, or --S(O).sub.p R.sup.3.
A particularly preferred class of compounds of formula (Ia) are those
having one or more of the following properties:
R represents hydrogen or --CO.sub.2 R.sup.3 ;
R.sup.1 represents cyclopropyl or 1-methylcyclopropyl;
R.sup.2 represents:
halogen;
a straight- or branched-chain alkyl group containing up to three carbon
atoms optionally substituted by one or more halogen atoms;
--S(O).sub.p R.sup.7 group;
--CH.sub.2 S(O).sub.q R.sup.7a ;
n represents zero, one or two;
R.sup.3 represents a straight- or branched-chain alkyl group containing
from one to three carbon atoms;
R.sup.7 represents methyl or ethyl optionally substituted by one or more
halogen atoms;
R.sup.7a represents a straight- or branched-chain alkyl group containing up
to four carbon atoms optionally substituted by one or more halogen atoms,
or phenyl optionally substituted by one or more halogen atoms or
--S(O).sub.p R.sup.7.
Another particularly preferred class of compounds of formula (Ia) are those
wherein:
R represents hydrogen, or --CO.sub.2 R.sup.3 ;
R.sup.1 represents cyclopropyl;
R.sup.2 represents:
halogen;
methyl optionally substituted by from one to three halogen atoms
(preferably fluorine);
nitro; or --S(O).sub.p CH.sub.3 ;
n represents zero, one or two; and
R.sup.3 represents methyl or ethyl.
Another particularly preferred class of compounds of formula (Ia) are those
wherein:
R represents hydrogen;
R.sup.1 represents cyclopropyl;
R.sup.2 represents:
methyl optionally substituted by from one to three halogen atoms
(preferably fluorine);
nitro; or --S(O).sub.p CH.sub.3 ;
n represents zero, one or two.
Particularly important compounds of formula (I) include the following:
1. 5-cyclopropyl-4-(4-pentafluorosulphanylbenzoyl) isoxazole;
2. 4-cyclopropylcarbonyl-5-(4-pentafluorosulphanylphenyl) isoxazole;
3. 2-cyano-3-cyclopropyl-1-(4-pentafluorosulphanylphenyl)propan-1,3-dione;
4. 5-cyclopropyl-4-(2-nitro-4-pentafluorosulphanylbenzoyl)isoxazole;
5. 5-cyclopropyl-4-(2-methylthio-4-pentafluorosulphanylbenzoyl)isoxazole;
6.
5-cyclopropyl-4-(2-methylsulphinyl-4-pentafluorosulphanylbenzoyl)isoxazole
;
7.
5-cyclopropyl-4-(2-methylsulphonyl-4-pentafluorosulphanylbenzoyl)isoxazole
;
110. 4-cyclopropylcarbonyl-5-(2-methylthio-
4-pentafluorosulphanylphenyl)isoxazole;
111.
2-cyano-3-cyclopropyl-1-(2-nitro-4-pentafluorosulphanylphenyl)propan-1,3-d
ione;
112. 2-cyano-3-cyclopropyl-1-(2-methylthio-
4-pentafluorosulphanylphenyl)propan-1,3-dione;
113.
2-cyano-3-cyclopropyl-1-(2-methylsulphonyl-4-pentafluorosulphanylphenyl)pr
opan-1,3-dione;
114.
2-cyano-3-cyclopropyl-1-(2-methylsulphinyl-4-pentafluorosulphanylphenyl)pr
opan-1,3-dione; and
115.
4-cyclopropylcarbonyl-5-(2-methylsulphonyl-4-pentafluorosulphanylphenyl)is
oxazole.
The following compounds of formula (Ia) in which the SF.sub.5 group is
attached to the 4-position of the phenyl ring form part of the present
invention.
In the table that follows "Me" means methyl, "Et" means ethyl, "c-Pr" means
cyclopropyl, "Ph" means phenyl. Where subscripts do not appear in the
Table it is understood that in appropriate cases they are present. For
example, "CF.sub.3 " is understood to mean --CF.sub.3 ; "NO2" is
understood to mean --NO.sub.2, etc.
______________________________________
Cpd. No. R R1 (R2)n
______________________________________
4 H c-Pr 2-NO2
5 H c-Pr 2-SMe
6 H c-Pr 2-SOMe
7 H c-Pr 2-SO2Me
8 H 1-Me-c-Pr 2-SMe
9 H 1-Me-c-Pr 2-SOMe
10 H 1-Me-c-Pr 2-SO2Me
11 CO2Et c-Pr 2-SMe
12 CO2Et c-Pr 2-SOMe
13 CO2Et c-Pr 2-SO2Me
14 H c-Pr 2-CH2SMe
15 H c-Pr 2-CH2SOMe
16 H c-Pr 2-CH2SO2Me
17 H c-Pr 2-Cl
18 CO2Et c-Pr 2-Cl
19 H 1-Me-c-Pr 2-Cl
20 H c-Pr 2-SMe-3-Cl
21 H c-Pr 2-SOMe-3-Cl
22 H c-Pr 2-SO2Me-3-Cl
23 H c-Pr 2-SEt
24 H c-Pr 2-SOEt
25 H c-Pr 2-SO2Et
26 H c-Pr 2-SMe-3-Br
27 H c-Pr 2-SMe-3-F
28 H c-Pr 2-F-3-SMe
29 H c-Pr 2-SMe-3-OMe
30 H c-Pr 2-SOMe-3-OMe
31 H c-Pr 2-SO2Me-3-OMe
32 H c-Pr 2-SMe-3-SMe
33 H c-Pr 2-F
34 H c-Pr 2-Me
35 H c-Pr 2-Et
36 H c-Pr 2-OMe
37 H c-Pr 2-Me-3-Cl
38 H c-Pr 2-Me-3-F
39 H c-Pr 2-Me-3-SMe
40 H c-Pr 2-Me-3-SOMe
41 H c-Pr 2-Me-3-SO2Me
42 H c-Pr 2-OMe-3-SMe
43 H c-Pr 2-OMe-3-SOMe
44 H c-Pr 2-OMe-3-SO2Me
45 H c-Pr 2-CH2S(2-SMe-Ph)
46 H c-Pr 2-CH2S(2-SOMe-Ph)
47 H c-Pr 2-CH2S(2-SO2Me-Ph)
48 H c-Pr 2-CH2SPh
49 H c-Pr 2-CH2SOPh
50 H c-Pr 2-CH2SO2Ph
51 H c-Pr 2-Cl-3-OCH2CH2OMe
52 H c-Pr 2-Cl-3-CONMe2
53 H c-Pr 2-Cl-3-CO2Me
54 H c-Pr 2-NMeSO2Me
55 H c-Pr 2-OSO2Me
56 H c-Pr 2-NMeCO2Me
57 H c-Pr 2-CH2NMeSO2Me
58 H c-Pr 2-CH2NMeCO2Me
59 H c-Pr 2-CH2S-iBu
60 H c-Pr 2-CH2SO-iBu
61 H c-Pr 2-CH2SO2-iBu
______________________________________
The following compounds of formula (Ia) in which the --SF.sub.5 group is
attached to the 2-position of the phenyl ring also form part of the
present invention.
______________________________________
Cpd. No. R R1 (R2)n
______________________________________
62 H c-Pr 4-NO2
63 H c-Pr 4-Cl
64 H c-Pr 4-Br
65 H c-Pr 4-SMe
66 H c-Pr 4-SOMe
67 H c-Pr 4-SO2Me
68 H 1-Me-c-Pr 4-SMe
69 CO2Et c-Pr 4-SMe
70 CO2Et c-Pr 4-SOMe
71 CO2Et c-Pr 4-SO2Me
72 H 1-Me-c-Pr 4-SOMe
73 H 1-Me-c-Pr 4-SO2Me
74 H c-Pr 3-F-4SMe
75 H c-Pr 3-F-4-SOMe
76 H c-Pr 3-F-4-SO2Me
77 H c-Pr 3-OMe-4-SMe
78 H c-Pr 3-OMe-4-SOMe
79 H c-Pr 3-OMe-4-SO2Me
80 H c-Pr 3-SMe-4-SMe
81 H c-Pr 3-SMe-4-Cl
82 H c-Pr 3-SOMe-4-Cl
83 H c-Pr 3-SO2Me-4-Cl
84 H c-Pr 3-Cl-4-SMe
85 H c-Pr 3-Cl-4-SOMe
86 H c-Pr 3-Cl-4-SO2Me
87 H c-Pr 3-Me-4-SMe
88 H c-Pr 3-Me-4-SOMe
89 H c-Pr 3-Me-4-SO2Me
90 H c-Pr 3-SMe-4-Me
91 H c-Pr 3-SOMe-4-Me
92 H c-Pr 3-SO2Me-4-Me
93 H c-Pr 3-SMe-4-OMe
94 H c-Pr 3-SOMe-4-OMe
95 H c-Pr 3-SO2Me-4-OMe
96 H c-Pr 3-SMe
97 H c-Pr 3-SOMe
98 H c-Pr 3-SO2Me
99 H c-Pr 4-CH2SMe
100 H c-Pr 4-CH2SOMe
101 H c-Pr 4-CH2SO2Me
102 CO2Et c-Pr 3-F-4-SMe
103 CO2Et c-Pr 3-OMe-4-SMe
104 CO2Et c-Pr 3-SMe-4-SMe
105 CO2Et c-Pr 3-SMe-4-Cl
106 CO2Et c-Pr 3-Cl-4-SOMe
107 CO2Et c-Pr 3-Me-4-SOMe
108 CO2Et c-Pr 3-SO2Me-4-Me
109 CO2Et c-Pr 3-SO2Me
______________________________________
Compounds of formula (I) may be prepared by the application or adaptation
of known methods (i.e. methods heretofore used or described in the
literature), for example as hereinafter described.
In the following description where symbols appearing in formulae are not
specifically defined, it is to be understood that they are "hereinbefore
defined" in accordance with the first definition of each symbol in the
specification.
It is to be understood that in the. descriptions of the following processes
the sequences may be performed in different orders, and that suitable
protecting groups may be required to achieve the compounds sought.
It is understood that when a process of the invention leads to the
formation of a mixture of (Ia) and (Ib), these compounds may be separated
by known methods.
According to a feature of the present invention compounds of formula (Ia)
or (Ib) in which R represents hydrogen and R.sup.1, R.sup.2 and n are as
defined above may be prepared by the reaction of a compound of formula
(II):
##STR3##
wherein L is a leaving group and R.sup.1, R.sup.2 and n are as hereinbefore
defined, with hydroxylamine or a salt of hydroxylamine. Hydroxylamine
hydrochloride is generally preferred. Generally L is alkoxy, for example
ethoxy, or N,N-dialkylamino, for example dimethylamino. The reaction is
generally is carried out in an organic solvent such as ethanol or
acetonitrile or a mixture of a water-miscible organic solvent and water,
preferably in a ratio of organic solvent: water of from 1:99 to 99:1,
optionally in the presence of a base or acid acceptor such as
triethylamine or sodium acetate at a temperature from room temperature to
the boiling point of the solvent.
Intermediates of formula (II) are novel and as such form a further feature
of the invention.
According to a further feature of the present invention compounds of
formula (Ia) in which R represents hydrogen and R.sup.1, R.sup.2 and n are
as defined above may be prepared by the reaction of a compound of formula
(III):
##STR4##
wherein R.sup.1 is as hereinbefore defined and Y, represents a carboxy
group or a reactive derivative thereof (such as a carboxylic acid chloride
or carboxylic ester), or a cyano group, with an appropriate organometallic
reagent such as a Grignard reagent or an organolithium reagent. The
reaction is generally carried out in an inert solvent such as ether or
tetrahydrofuran at a temperature from 0.degree. C. to the reflux
temperature of the mixture.
According to a further feature of the present invention compounds of
formula (Ia) wherein R represents a group --CO.sub.2 R.sup.3 and R.sup.1
R.sup.2 and n are as defined above, may be prepared by the reaction of a
compound of formula (IV):
##STR5##
wherein R.sup.1, R.sup.2 and n are as hereinbefore defined and P.sup.1 is a
leaving group such as N,N-dialkylamino, with a compound of formula R.sup.3
O.sub.2 CC(Z.sup.1).dbd.NOH wherein R.sup.3 is as hereinbefore defined and
Z.sup.1 is a halogen atom. Generally Z.sup.1 is chlorine or bromine. The
reaction is generally performed in an inert solvent such as toluene or
dichloromethane either in the presence of a base such as triethylamine or
a catalyst such as a 4 Angstrom molecular sieve or fluoride ion.
Intermediates of formula (IV) are novel and as such form a further feature
of the invention.
According to a further feature of the present invention compounds of
formula (Ia) in which R represents a group --CO.sub.2 R.sup.3 and R.sup.1,
R.sup.2 and n are as defined above may be prepared by the reaction of a
compound of formula (V):
##STR6##
wherein R.sup.1, R.sup.2 and n are as hereinbefore defined, with a compound
of formula R.sup.3 O.sub.2 CC(Z.sup.1).dbd.NOH wherein Z.sup.1 and R.sup.3
are as hereinbefore defined. The reaction is generally performed in an
inert solvent such as toluene or dichloromethane optionally in the
presence of a base such as triethylamine or a catalyst such as a 4
Angstrom molecular sieve or fluoride ion. The reaction is preferably
carried out at a temperature between room temperature and the reflux
temperature of the mixture. Intermediates of formula (V) are novel and as
such form a further feature of the invention.
According to a further feature of the present invention compounds of
formula (Ia) or (Ib) wherein R represents --CO.sub.2 R.sup.3 and R.sup.1,
R.sup.2 and n are as defined above, may be prepared by the reaction of a
salt of compounds of formula (VI):
##STR7##
wherein R.sup.1, R.sup.2 and n are as hereinbefore defined with a compound
of formula R.sup.3 O.sub.2 CC(Z.sup.1).dbd.NOH wherein R.sup.3 and Z.sup.1
are as hereinbefore defined. Preferred salts include sodium or magnesium
salts. The reaction is generally performed in an inert solvent such as
dichloromethane or acetonitrile at a temperature between room temperature
and the reflux temperature of the mixture. The salt of a compound of
formula (VI) is generally prepared in situ by treating the compound of
formula (VI) with a base. Examples of suitable bases include alkaline
earth metal alkoxides such as magnesium methoxide. Intermediates of
formula (VI) are novel and as such form a further feature of the
invention.
According to a feature of the present invention compounds of formula (Ib)
in which R, R.sup.1, R.sup.2 and n are as defined above, may be prepared
by the metallation of a compound of general formula (VII):
##STR8##
wherein R, R and n are as defined above and A is a halogen atom, followed
by reaction of the compound thus obtained with an acid chloride of formula
R.sup.1 COCl wherein R.sup.1 is as defined above. Generally A is bromine
or iodine and the reaction performed with for example n- butyllithium in
an inert solvent such as ether or tetrahydrofuran at a temperature from
-78.degree. C. to 0.degree. C. Compounds of formula (VII) are novel and as
such constitute a further feature of the invention.
According to a further feature of the present invention compounds of
formula (Ib) in which R, R.sup.1, R.sup.2 and n are as defined above may
be prepared by the oxidation of a compound of formula (VIII):
##STR9##
wherein R, R.sup.1, R.sup.2 and n are as defined above, to convert the
hydroxy group to a ketone group. The reaction is generally performed using
an appropriate oxidising agent, for example, a mixture prepared from
chromium trioxide and aqueous sulphuric acid. Compounds of formula (VIII)
are novel and as such constitute a further feature of the invention.
According to a further feature of the present invention compounds of
formula (Ib) in which R represents hydrogen and R.sup.1, R.sup.2 and n are
as defined above may be prepared by the reaction of a compound of formula
(IX):
##STR10##
in which R.sup.2 and n are as defined above and D represents a carboxy
group, or a reactive derivative thereof (such as a carboxylic acid
chloride or carboxylic ester), or a cyano group, with an appropriate
organometallic reagent such as a Grignard reagent or an organolithium
reagent. The reaction is generally carried out in an inert solvent such as
ether or tetrahydrofuran, at a temperature from 0.degree. C. to the reflux
temperature of the solvent. Intermediates of formula (IX) are novel and as
such form a further feature of the invention.
According to a further feature of the present invention compounds of
formula (Ib) in which R represents a --CO.sub.2 R.sup.3 group and R.sup.1,
R.sup.2 and n are as defined above, may be prepared by the reaction of a
compound of general formula (X):
##STR11##
wherein R.sup.1, R.sup.2 and n are as defined and P.sup.1 is as defined
above, with a compound of formula R.sup.3 O.sub.2 CC(Z.sup.1).dbd.NOH
wherein Z.sup.1 and R.sup.3 are as hereinbefore defined. Generally Z.sup.1
is chlorine or bromine. The reaction is preferably performed in an inert
solvent such as toluene or dichloromethane either in the presence of a
base such as triethylamine or a catalyst such as a 4 Angstrom molecular
sieve or fluoride ion. Intermediates of formula (X) are novel and as such
form a further feature of the invention.
According to a further feature of the present invention compounds of
formula (Ib) in which R represents a group --CO.sub.2 R.sup.3 and R.sup.1,
R.sup.2 and n are as defined above may be prepared by the reaction of a
compound of formula (XI):
##STR12##
wherein R.sup.1,R.sup.2 and n are as defined above, with a compound of
formula R.sup.3 O.sub.2 CC(Z.sup.1).dbd.NOH wherein Z.sup.1 and R.sup.3
are as hereinbefore defined. Generally Z.sup.1 is chlorine or bromine. The
reaction is preferably performed in an inert solvent such as toluene or
dichloromethane, either in the presence of a base such as triethylamine,
or a catalyst such as a 4 Angstrom molecular sieve or fluoride ion.
Intermediates of formula (XI) are novel and as such form a futher feature
of the invention.
According to a feature of the present invention compounds of formula (IC)
may be prepared from the corresponding compound of formula (Ia) or (Ib) in
which R is as defined above, or in which R is replaced by an amide or
nitrile. Where R represents a hydrogen atom the reaction is preferably
carried out by treatment with a base. Examples of suitable bases include
alkali or alkaline earth metal hydroxides, alkoxides such as sodium
ethoxide or organic bases such as triethylamine. Where R-represents
--CO.sub.2 R.sup.3, or where R is replaced by amide or nitrile, the
conversion is generally carried out by a hydrolytic reaction. The
hydrolytic reaction may be performed in the presence of an acid or base.
Acidic hydrolysis may be achieved for example using aqueous hydrochloric
acid. Basic hydrolysis may be achieved for example using sodium hydroxide
in a mixture of alcohol and water. The reactions are preferably carried
out at a temperature between room temperature and the reflux temperature
of the mixture. Compounds of formula (Ia) or (Ib) in which R is replaced
by amide or nitrile are novel and thus constitute a further feature of the
invention.
According to a further feature of the present invention, compounds of
formula (IC) in which R.sup.1, R.sup.2 and n are as defined above may also
be prepared by the reaction of a benzoyl chloride of formula (XII):
##STR13##
wherein R.sup.2 and n are as hereinbefore defined, with a beta-ketonitrile
of formula (XIII):
##STR14##
wherein R.sup.1 is as hereinbefore defined. The reaction is generally
performed in the presence of a base, in a solvent or solvent mixture.
Suitable bases include metal hydrides, hydroxides or alkoxides (e.g.
sodium or lithium hydride, sodium hydroxide, potassium hydroxide,
magnesium ethoxide or magnesium methoxide). Suitable solvents include for
example tetrahydrofuran; hydrocarbons such as toluene; or halogenated
hydrocarbons such as dichloromethane. The reaction is generally performed
at a temperature from 0.degree. C. to the reflux temperature. A number of
compounds of formula (XII) are novel and thus form a further feature of
the invention.
According to a further feature of the present invention, compounds of
formula (Ic) in which R.sup.1, R.sup.2 and n are as defined above may also
be prepared by the reaction of an acid chloride of formula R.sup.1 COCl
wherein R.sup.1 is as hereinbefore defined, with a beta-ketonitrile of
formula (XIV):
##STR15##
wherein R.sup.2 and n are as hereinbefore defined. The reaction is
generally performed under the same conditions as described above for the
reaction of compounds of formula (XII) with compounds of formula (XIII).
Intermediates of formula (XIV) are novel and as such form a further
feature of the invention.
According to a further feature of the present invention compounds of
formula (Ic) in which R.sup.1, R.sup.2 and n are as defined above may also
be prepared by the reaction of a benzoyl chloride of formula (XII) above
wherein R.sup.2 and n are as hereinbefore defined, with a beta-ketonitrile
of formula (XIII) wherein R.sup.1 is as hereinbefore defined, via an
intermediate of formula (XV):
##STR16##
wherein R.sup.1, R.sup.2 and n are as hereinbefore defined. The formation
of the intermediate of formula (XV) may be carried out in the presence of
a mild base such as an organic base e.g. triethylamine, in an inert
solvent such as acetonitrile or dichloromethane at a temperature between
room temperature and the reflux temperature of the mixture. The
rearrangement of the intermediate of formula (XV) to a compound of formula
(Ic) is generally carried out in situ in an inert solvent such as
acetonitrile or dichloromethane in the presence of a catalyst such as a
source of cyanide. Examples of such sources of cyanide are acetone
cyanohydrin or an alkali metal cyanide such as potassium cyanide,
optionally in the presence of a crown ether such as 18-crown-6.
Intermediates of formula (XV) are novel and as such constitute a further
feature of the invention.
According to a further feature of the present invention compounds of
formula (Ic) in which R.sup.1, R.sup.2 and n are as defined above, may be
prepared by the reaction of an acid chloride of formula R.sup.1 COCl
wherein R.sup.1 is as hereinbefore defined, with a beta-ketonitrile of
formula (XIV) wherein R.sup.2 and n are as hereinbefore defined via an
intermediate of formula (XVI):
##STR17##
wherein R.sup.1, R.sup.2 and n are as hereinbefore defined. The formation
and rearrangement of the intermediate of formula (XVI) is generally
carried out under the same conditions as described above for the formation
and rearrangement of compounds of formula (XV). Intermediates of formula
(XVI) are novel and as such form a further feature of the invention.
Intermediates in the preparation of compounds of formula (Ia), (Ib) and
(Ic) may be prepared by the application or adaptation of known methods.
Intermediates of formula (Ia) or (Ib) in which R is replaced by an amide or
nitrile may be prepared by the reaction of a salt of a compound of formula
(VI) with a compound of formula P.sup.2 C(Z.sup.1).dbd.NOH in which
P.sup.2 is amide or nitrile. The reaction is performed using the same
conditions as described for the preparation of compounds of formula (Ia)
or (Ib) in which R is --CO.sub.2 R.sup.3 from compounds of formula (VI).
Compounds of formula (II) may be prepared by the reaction of compounds of
formula (VI) with either a trialkyl orthoformate such as triethyl
orthoformate or a dimethylformamide dialkyl acetal such as
dimethylformamide dimethyl acetal. The reaction with a trialkyl
orthoformate can be carried out in the presence of acetic anhydride at the
reflux temperature of the mixture and the reaction with dialkylformamide
dialkyl acetal is carried out optionally in the presence of an inert
solvent at a temperature from room temperature to the reflux temperature
of the mixture.
Compounds of formula (IV) may be prepared by the reaction of a compound of
formula (XVII) with a benzoyl chloride of formula (XII):
R.sup.1 C(P.sup.1).dbd.CH.sub.2 (XVII)
wherein R.sup.1 and P.sup.1 are as defined above.
The reaction is generally carried out in the presence of an organic base
such as triethylamine in an inert solvent such as toluene or
dichloromethane at a temperature between -20.degree. C. and room
temperature.
Compounds of formula (V) may be prepared by the metallation of the
appropriate acetylene of formula (XVIII):
R.sup.1 .tbd.CH (XVIII)
followed by reaction of the metal salt thus obtained with a benzoyl
chloride of formula (XII). The metallation is generally performed using
n-butyl lithium in an inert solvent such as ether or tetrahydrofuran at a
temperature from -78.degree. C. to 0.degree. C. The subsequent reaction
with the benzoyl chloride is carried out in the same solvent at a
temperature between --78.degree. C. and room temperature.
Compounds of formula (VI) may be prepared by the reaction of an acid
chloride of formula (XII) with the metal salt of a compound of formula
(XIX):
##STR18##
wherein R.sup.1 is as hereinbefore defined, to give a compound of formula
(XX):
##STR19##
wherein R.sup.1, R.sup.2 and n are as hereinbefore defined, which is
subsequently decarboxylated to give a compound of formula (VI). Generally
the reaction to produce the compound of formula (XX) is performed in a
solvent such as a lower alcohol, preferably methanol, in the presence of a
metal, preferably magnesium. The reaction may also be performed using a
pre-prepared metal salt of a compound of formula (XIX). The
decarboxylation is generally performed by refluxing the compound of
formula (XX) in the presence of a catalyst, such as para-toluenesulphonic
acid or trifluoroacetic acid, in an inert solvent e.g. toluene or
1,2-dichloroethane.
Compounds of formula (VI) may also be prepared by the reaction of a benzoic
acid ester of formula (XXI):
##STR20##
wherein R.sup.2 and n are as hereinbefore defined and R.sup.15 represents
straight- or branched-chain C.sub.1-6 alkyl, with a compound of formula
(XXII):
R.sup.1 --C(O)--CH.sub.3 (XXII)
wherein R.sup.1 is as hereinbefore defined. The reaction is generally
performed in a solvent such as ether, tetrahydrofuran or N,N-
dimethylformamide, in the presence of a base, preferably an alkali metal
base such as sodium hydride, at a temperature from 0.degree. C. to the
reflux temperature.
Acid chlorides of formula (XII) may be prepared by the reaction of a
benzoic acid of formula (XXIII):
##STR21##
with a chlorinating agent, for example thionyl chloride at the reflux
temperature of the mixture. In some cases the benzoyl chlorides may also
be prepared by reaction of the benzoic acid with oxalyl chloride in a
solvent such as 1,2-dichloroethane at from ambient to reflux temperature.
Benzoic acids of formula (XXIII) are novel with the exclusion of those in
which n is zero and the --SFs group is located m- or p- to the carboxy
group (these compounds being reported by W. A. Sheppard in J.Am.Chem.Soc.
1962, 84, 3064-3072) and as such constitute a further feature of the
present invention.
Esters of formula (XXI) are novel and as such constitute a further feature
of the present invention.
Esters of formula (XXI) may be prepared from acids of formula (XXIII) by
known methods.
Compounds of general formula (VIII) may be prepared by metallation of
compounds of general formula (VII) wherein A represents bromine or iodine
with for example n-butyllithium in an inert solvent such as ether or
tetrahydrofuran at a temperature from -78.degree. C. to 0.degree. C.,
followed by reaction with an aldehyde of general formula R.sup.1 CHO.
Compounds of general formula (IX) wherein D is --CO.sub.2 -alkyl or --CN
may be prepared by the reaction of compounds of general formula (XXIV):
##STR22##
wherein D' represents CO.sub.2 -alkyl or --CN and L is as hereinbefore
defined, with a salt of hydroxylamine such as hydroxylamine hydrochloride,
in a solvent such as ethanol or acetonitrile, optionally in the presence
of a base or acid acceptor such as triethylamine or sodium acetate.
Compounds of general formula (IX) in which D represents a carboxylic acid
or carboxylic acid chloride may be prepared from the corresponding
compound of general formula (IX) in which D represents a carboxylic ester
group by the hydrolysis of said ester group and conversion, as necessary,
of the acid thus obtained to the acid chloride, e.g. by heating with
thionyl chloride.
Compounds of general formula (XXIV) may be prepared by the reaction of a
ketoester or ketonitrile of general formula (XXV):
##STR23##
with either triethyl orthoformate in the presence of acetic anhydride at
the reflux temperature of the mixture or with dimethylformamide
dimethylacetal optionally in an inert solvent such as toluene at a
temperature from room temperature to the reflux temperature of the
mixture.
Compounds of general formula (X) may be prepared by the reaction of a
compound of general formula (XXVI):
##STR24##
wherein P.sup.1 is as hereinbefore defined, with an acid chloride of
general formula R.sup.1 COCl in an inert solvent such as dichloromethane
or toluene, in the presence of a base such as triethylamine.
Compounds of general formula (XI) may be prepared by the metallation of the
appropriate phenylacetylene of general formula (XXVII):
##STR25##
wherein Q represents hydrogen or a bromine or iodine atom, using for
example n-butyllithium in an inert solvent such as ether or
tetrahydrofuran at a temperature from -78.degree. C. to 0.degree. C.,
followed by treatment with an acid chloride of general formula R.sup.1
COCl.
Compounds of general formula (VII) may be prepared by the halogenation of
compounds of general formula (XXVIII):
##STR26##
for example by heating with bromine or iodine in the presence of
concentrated nitric acid.
Compounds of general formula (XXVIII) may be prepared by the reaction of
compounds of general formula (XXIX):
##STR27##
with a salt of hydroxylamine such as hydrochloride, in a solvent such as
ethanol or acetonitrile, optionally in the presence of a base or acid
acceptor such as triethylamine or sodium acetate.
Beta-ketonitriles of formula (XIII) may be prepared from acid chlorides of
formula R.sup.1 COCl by a number of methods well known in the chemical
literature. For example, see Krauss, et al, Synthesis, 1983, 308, or Muth,
et al, J. Org. Chem, 1960, 25, 736. Alternatively beta-ketonitriles of
formula (XIII) may be prepared by the reaction of an ester of formula
R.sup.1 --CO.sub.2 Et, wherein R.sup.1 is as hereinbefore defined, with
acetonitrile. This reaction is described in the literature, for example
see the article by Abramovitch and Hauser, J.Am. Chem. Soc., 1942, 64,
2720.
Beta-ketonitriles of formula (XIV) may be prepared from benzoyl chlorides
of formula (XII) or from corresponding ethyl benzoates in a manner
analogous to the preparation of beta- ketonitriles of formula (XIII) set
forth above.
According to a further feature of the invention benzoic acids of formula
(XXIII) may be prepared by the reaction of a compound of formula (XXX):
##STR28##
wherein X represents an iodine, chlorine or preferably bromine atom and
R.sup.2 is as defined above, with an organometallic reagent, generally a
Grignard or organolithium reagent. Preferably n-butyl lithium is employed
(in which case X is an iodine or bromine atom) in an inert solvent, for
example ether at a temperature from -78.degree. C. to 20.degree. C.,
followed by reaction with carbon dioxide or a source thereof.
The intermediate halides of formula (XXX) may be prepared according to
known methods, for example as described in J.Am.Chem.Soc. 84, 3064 (1962).
Intermediates of formula (III), (XVII), (XVIII), (XIX) and (XXII) are known
or may be prepared by the application or adaptation of known methods.
Those skilled in the art will appreciate that some compounds of formula (I)
may be prepared by the interconversion of other compounds of formula (I)
and such interconversions constitute yet more features of the present
invention.
According to a further feature of the present invention compounds in which
p or q is one or two may be prepared by the oxidation of the sulphur atom
of the corresponding compounds in which p or q is zero or one. The
oxidation of the sulphur atom is generally carried out using for example
3-chloroperoxybenzoic acid in an inert solvent such as dichloromethane at
a temperature from -40.degree. C. to room temperature.
Agriculturally acceptable salts or metal complexes of compounds of formulae
(Ia), (Ib) or (Ic) can be prepared using known methods, or by the
application of known methods.
The following non-limiting Examples illustrate the preparation of compounds
of formula (I) and the Reference Examples illustrate the preparation of
intermediates in their synthesis. NMR Spectra are recorded as 3 (ppm) in
deuterochloroform as solvent.
EXAMPLE 1
Hydroxylamine hydrochloride (0.42 g) was added to a stirred solution of
3-cyclopropyl-2-ethoxymethylene-1-(4-pentafluorosulphanyl-
phenyl)-propan-1,3-dione (0.97 g) in ethanol. Anhydrous sodium acetate
(0.49 g) was then added and stirring maintained for 1 hour. The solvent
was evaporated and the residue distributed between dichloromethane and
water. The organic phase was dried (magnesium sulphate) and evaporated,
and the residual oil purified by chromatography eluting with ethyl
acetate/hexane to give after trituration with hexane
5-cyclopropyl-4-(4-pentafluorosulphanyl- benzoyl)isoxazole (Compound 1) as
a white solid, m.p.57-58.degree. C. Further elution gave, after
trituration with hexane, 4-cyclopropylcarbonyl-
5-(4-pentafluorosulphanylphenyl)isoxazole (Compound 2) as a white solid,
m.p.53-55.degree. C.
The following compounds were prepared in a similar manner:
5-cyclopropyl-4-(2-methylthio-4-pentafluorosulphanylbenzoyl)isoxazole
(Compound 5), m.p.80-81.degree. C. and
4-cyclopropylcarbonyl-5-(2-methylthio-4-pentafluorosulphanylphenyl)isoxazo
le (Compound 110), NMR 0.98 (m,2H), 1.21 (m,2H), 2.0 (m,1H), 2.5 (s,3H),
7.58 (d,1H), 7.68-7.73 (m,2H), 8.8 (s,1H); and
5-cyclopropyl-4-(2-nitro-4-pentafluorosulphanylbenzoyl)isoxazole (Compound
4),m.p. 132-133.degree. C.
EXAMPLE 2
Triethylamine (0.73 g) was added to a stirred solution of
4-cyclopropylcarbonyl-5-(4-pentafluorosulphanylphenyl)isoxazole (Compound
2, 0.4 g) in dichloromethane. After 16 hours the solution was washed (2M
hydrochloric acid), dried (magnesium sulphate) and evaporated to dryness.
The residue was purified by chromatography eluting with ethyl
acetate/hexane to give a residue which was suspended in dichloromethane
and shaken with hydrochloric acid until dissolved. The organic phase was
evaporated and triturated with hexane to give
2-cyano-3-cyclopropyl-1-(4-pentafluorosulphanylphenyl)propan-1,3-dione as
a white solid (Compound 3, m.p.108-110.degree. C.
The following compounds were prepared in a similar manner:
2-cyano-3-cyclopropyl-1-(2-nitro-4-pentafluorosulphanylphenyl)propan-1,3-di
one (Compound 111), m.p.120-121.degree. C.;
2-cyano-3-cyclopropyl-1-(2-methylthio-4-pentafluorosulphanylphenyl)propan-1
,3-dione (Compound 112), m.p.93.degree. C.;
2-cyano-3-cyclopropyl-1-(2-methylsulphonyl-
4-pentafluorosulphanylphenyl)propan-1,3-dione (Compound 113),
m.p.189-190.degree. C.; and
2-cyano-3-cyclopropyl-1-(2-methylsulphinyl-
4-pentafluorosulphanylphenyl)propan-1,3-dione (Compound 114),
m.p.146-148.degree. C.
EXAMPLE 3
3-Chloroperbenzoic acid (0.95 g of 70%) was added to a solution of
5-cyclopropyl-4-(2-methylthio-4-pentafluorosulphanyl- benzoyl)isoxazole
(0.6 g) in dichloromethane and stirred overnight at 20.degree. C., cooled,
filtered and the filtrate washed in turn with sodium metabisulphite
solution, sodium acetate solution and water. The organic phase was dried
(magnesium sulphate), evaporated and the residue washed (hexane) to give
5-cyclopropyl-4-(2-methylsulphonyl-4-pentafluorosulphanylbenzoyl)isoxazole
(0.37 g, Compound 7), m.p.168-170.degree. C.
By proceeding in a similar manner but employing the appropriate amount of
3-chloroperbenzoic acid there was obtained:
5-cyclopropyl-4-(2-methylsulphinyl-4-pentafluorosulphanylbenzoyl)isoxazole
(0.37 g, Compound 6), m.p.174-175.degree. C.
EXAMPLE 4
By proceeding according to the method of Example 3 there was prepared from
4-cyclopropylcarbonyl-5-(2-methylthio-4-pentafluorosulphanylphenyl)isoxazo
le the following compound:
4-cyclopropylcarbonyl-5-(2-methylsulphonyl-
4-pentafluorosulphanylphenyl)isoxazole (Compound 115), m.p.143-145.degree.
C.
REFERENCE EXAMPLE 1
A mixture of
3-cyclopropyl-1-(4-pentafluorosulphanylphenyl)-propan-1,3-dione (0.82 g)
and triethylorthoformate (3.1 g) in acetic anhydride (40 ml) was heated at
reflux temperature for 6 hours. The excess reagent and solvent were
evaporated to give
3-cyclopropyl-2-ethoxymethylene-1-(4-pentafluorosulphanylphenyl)-propan-1,
3-dione (1.0 g) as an orange oil. This was used directly in the subsequent
reaction stage.
By proceeding in a similar manner the following compounds were prepared:
3-cyclopropyl-2-ethoxymethylene-1-(2-methylthio-4-pentafluorosulphanylpheny
l) propan- 1,3-dione; and
3-cyclopropyl-2-ethoxymethylene-1-(2-nitro-4-pentafluorosulphanylphenyl)pro
pan-1,3-dione.
REFERENCE EXAMPLE 2
A solution of t-butyl 3-cyclopropyl-3-oxopropionate magnesium enolate (1.43
g, prepared from t-butyl 3-cyclopropyl-3-oxopropionate and magnesium
turnings in methanol) in toluene was stirred at room temperature. A
solution of 4-pentafluorosulphanylbenzoyl chloride (1.07 g) in toluene was
added. After 2 hours, hydrochloric acid (2 M) was added and the mixture
vigorously stirred for 15 minutes. The organic phase was dried by
azeotropic removal of solvent. 4-Toluenesulphonic acid (0.1 g) was added
and the solution heated at reflux for 3.5 hours. The cooled solution was
washed (water), dried (magnesium sulphate) and evaporated. Purification of
the residue by chromatography, eluting with ethyl acetate/hexane gave
3-cyclopropyl-1-(4-pentafluorosulphanylphenyl)propan-1,3-dione as a fawn
solid (1.0 g), m.p.70-72.degree. C.
By proceeding in a similar manner the following compounds were prepared:
3-cyclopropyl-1-(2-methylthio-4-pentafluorosulphanylphenyl)propan-1,3-dione
, NMR 1.02 (m,2H), 1.25 (m,2H), 1.8 (m,1H), 2.52 (s,3H), 6.11 (s,2H),
7.55-7.65 (m,3H); and
3-cyclopropyl-1-(2-nitro-4-pentafluorosulphanylphenyl)propan-1,3-dione,
m.p.108-110.degree. C.
REFERENCE EXAMPLE 3
Oxalyl chloride (1.53 g) was added to a stirred solution of
4-pentafluorosulphanyl- benzoic acid (0.99 g) in dichloroethane. A
solution of N,N-dimethylformamide in dichloromethane (3 ml of a solution
prepared by the addition of 2 drops of N,N-dimethylformamide to 10 ml of
dichloromethane) was added. After 15 minutes the solution was heated for a
further 15 minutes at 45.degree. C., and evaporated to dryness to give
4-pentafluorosulphanylbenzoyl chloride as an orange oil (1.07 g). This was
used directly in the subsequent reaction stage.
By proceeding in a similar manner the following compounds were prepared:
2-methylthio-4-pentafluorosulphanylbenzoyl chloride; and
2-nitro-4-pentafluorosulphanylbenzoyl chloride.
REFERENCE EXAMPLE 4
A solution of n-butyllithium (9.4 ml of a 1.6 M solution in hexane) was
added to a stirred solution of 4-bromophenylsulphur pentafluoride (3.87 g)
in ether at -78.degree. C. under an inert atmosphere. After maintaining at
-78.degree. C. for 1 hour, solid carbon dioxide (20 g) was added and the
mixture allowed to warm to 5.degree. C. during 1.5 hours. Hydrochloric
acid (2 M) was added, the mixture stirred for 0.5 hour and the organic
phase separated and itself extracted with sodium carbonate solution. The
basic extract was washed (ether) and acidified (hydrochloric acid). The
precipitated solid was extracted (ether), dried (magnesium sulphate) and
evaporated. The residue was triturated (hexane) to give
4-pentafluorosulphanylbenzoic acid as a fawn solid (1.2 g),
m.p.188-190.degree. C.
REFERENCE EXAMPLE 5
A solution of 4-aminophenylsulphur pentafluoride (4.38 g) in acetonitrile
was added dropwise at -2.degree. C. to 1.degree. C. during 15 minutes to a
stirred mixture of copper (II) bromide (4.46 g) and t-butyl nitrite (5.15
g) in acetonitrile. Stirring was continued at 0.degree. C. for 15 minutes
and then at ambient temperature for 4 hours. The mixture was poured into
water, acidified to pH 1 with 2 M hydrochloric acid, and extracted
(ether). The extract was washed (water), dried (magnesium sulphate) and
evaporated to dryness to give 4-bromophenylsulphur pentafluoride as a dark
oil (5.9 g), NMR (CDCl.sub.3) 7.66 (s,4H).
By proceeding in a similar manner 4-bromo-3-nitrophenylsulphur
pentafluoride as an orange oil was prepared, single peak by gas
chromatography (Megabore OV1 type column).
REFERENCE EXAMPLE 6
A mixture of 2-methylthio-4-pentafluorosulphanylbenzonitrile (0.47 g) and
sodium hydroxide (0.2 g) in a mixture of water and ethylene glycol (1:5)
was heated at reflux for 5 hours. The cooled mixture was diluted (water),
acidified (hydrochloric acid) and the solid filtered, washed (water) and
dried to give 2-methylthio-4-pentafluorosulphanylbenzoic acid (0.38 g),
m.p.150-152.degree. C.
REFERENCE EXAMPLE 7
2--Nitro-4-pentafluorosulphanylbenzonitrile (6.6 g) was added to a mixture
of water and sulphuric acid (1:1) and the mixture stirred and heated at
reflux for 3.5 hours. The cooled mixture was poured onto ice/water,
extracted (ether) and the organic phase then extracted into sodium
carbonate solution (2N). The basic extract was washed (ether), acidified
(hydrochloric acid) and extracted (ether). The ethereal layer was washed
(water), dried (magnesium sulphate) and evaporated to give
2-nitro-4-pentafluorosulphanylbenzoic acid. (5.97 g), m.p.165-167.degree.
C.
REFERENCE EXAMPLE 8
Sodium thiomethoxide (8.97 g) was added to a solution of
2-nitro-4-pentafluorosulphanylbenzonitrile (11.7 g) in acetone and stirred
at 20.degree. C. overnight, then evaporated and purified by column
chromatography on silica gel eluting with ethyl acetate/hexane (3:97) to
give 2-methylthio-4-pentafluorosulphanylbenzonitrile (4.65 g),
m.p.101-102.degree. C.
REFERENCE EXAMPLE 9
Copper (I) cyanide (5.05 g) was added to a stirred solution of
4-bromo-3-nitro- phenylsulphur pentafluoride (18.5 g) in N,N-
dimethylformamide and heated at 140.degree. C. for 4 hours. A mixture of
ferric chloride (20.0 g),concentrated hydrochloric acid and water was
added at 105.degree. C. and heating continued for 1.25 hours. The cooled
mixture was diluted with water, extracted (ether) and the organic phase
washed (water), dried (magnesium sulphate) and evaporated to give
2-nitro-4-pentafluorosulphanylbenzonitrile (14.7 g), m.p.57-59.degree. C.
REFERENCE EXAMPLE 10
4-Acetamido-3-nitrophenylsulphur pentafluoride (29.0 g) was heated at
reflux with hydrochloric acid (6N) and dioxan for 40 minutes and
concentrated to low volume, basified with sodium carbonate solution and
extracted (ether). The extract was washed (water), dried (magnesium
sulphate) and evaporated to give 4-amino-3-nitrophenylsulphur
pentafluoride (24.7 g), m.p.132-135.degree. C.
REFERENCE EXAMPLE 11
4-Acetamidophenylsulphur pentafluoride (27.0 g) was added during 5 minutes
to a stirred mixture of concentrated nitric acid and concentrated
sulphuric acid (1 part:2 parts by volume) at 0-5.degree. C. After 5
minutes acetic acid (1 part) was added and stirring continued at 5.degree.
C. for 1.5 hours. The mixture was added to ice/water, extracted (ethyl
acetate) and the extract washed (sodium carbonate solution), dried
(magnesium sulphate) and evaporated. The residue was triturated with ether
to give 4-acetamido-3-nitrophenylsulphur pentafluoride (30.0 g),
m.p.135-138.degree. C.
REFERENCE EXAMPLE 12
Acetic-anhydride was added during 5 minutes to a stirred solution of
4-aminophenylsulphur pentafluoride (30.2 g) in acetic acid at 40.degree.
C. and then heated at 65.degree. C. for 0.5 hour. The cooled mixture was
added to water, stirred for 1 hour and filtered. The solid was washed with
water, sodium bicarbonate solution and water, dried and purified by
stirring with hexane to give 4-acetamidophenylsulphur pentafluoride (27.0
g), m.p.131-132.degree. C.
According to a feature of the present invention, there is provided a method
for controlling the growth of weeds (i.e. undesired vegetation) at a locus
which comprises applying to the locus a herbicidally effective amount of
at least one isoxazole or 2-cyano-1,3-dione derivative of formula (I) or
an agriculturally acceptable salt or metal complex thereof. For this
purpose, the isoxazole or 2-cyano-1,3-dione derivatives are normally used
in the form of herbicidal compositions (i.e. in association with
compatible diluents or carriers and/or surface active agents suitable for
use in herbicidal compositions), for example as hereinafter described.
The compounds of formula (I) show herbicidal activity against
dicotyledonous (i.e. broad- leafed) and monocotyledonous (i.e. grass)
weeds by pre- and/or post-emergence application.
By the term "pre-emergence application" is meant application to the soil in
which the weed seeds or seedlings are present before emergence of the
weeds above the surface of the soil. By the term "post-emergence
application" is meant application to the aerial or exposed portions of the
weeds which have emerged above the surface of the soil.
For example, the compounds of formula (I) may be used to control the growth
of:
broad-leafed weeds, for example, Abutilon theophrasti, Amaranthus
retroflexus, Bidens pilosa, Chenopodium album, Galium aparine, Ipomoea
spp. e.g. Ipomoea purpurea, Sesbania exaltata, Sinapis arvensis, Solanum
nigrum and Xanthium strumarium, and
grass weeds, for example Alopecurus myosuroides, Avena fatua, Digitaria
sanguinalis, Echinochloa crus-galli, Sorghum bicolor, Eleusine indica and
Setaria spp, e.g. Setaria faberii or Setaria viridis, and
sedges, for example, Cyperus esculentus.
The amounts of compounds of formula (I) applied vary with the nature of the
weeds, the compositions used; the time of application, the climatic and
edaphic conditions and (when used to control the growth of weeds in
crop-growing areas) the nature of the crops. When applied to a
crop-growing area, the rate of application should be sufficient to control
the growth of weeds without causing substantial permanent damage to the
crop. In general, taking these factors into account, application rates
between 0.01 kg and 5 kg of active material per hectare give good results.
However, it is to be understood that higher or lower application rates may
be used, depending upon the particular problem of weed control
encountered.
The compounds of formula (I) may be used to control selectively the growth
of weeds, for example to control the growth of those species hereinbefore
mentioned, by pre- or post-emergence application in a directional or non-
directional fashion, e.g. by directional or non-directional spraying, to a
locus of weed infestation which is an area used, or to be used, for
growing crops, for example cereals, e.g. wheat, barley, oats, maize and
rice, soya beans, field and dwarf beans, peas, lucerne, cotton, peanuts,
flax, onions, carrots, cabbage, oilseed rape, sunflower, sugar beet, and
permanent or sown grassland before or after sowing of the crop or before
or after emergence of the crop. For the selective control of weeds at a
locus of weed infestation which is an area used, or to be used, for
growing of crops, e.g. the crops hereinbefore mentioned, application rates
between 0.01 kg and 4.0 kg, and preferably between 0.01 kg and 1.0 kg,
more preferably from 0.01 kg to 0.5 kg of active material per hectare are
particularly suitable.
The compounds of formula (I) may also be used to control the growth of
weeds, especially those indicated above, by pre- or post-emergence
application in established orchards and other tree-growing areas, for
example forests, woods and parks, and plantations, e.g. sugar cane, oil
palm and rubber plantations. For this purpose they may be applied in a
directional or non- directional fashion (e.g. by directional or non-
directional spraying) to the weeds or to the soil in which they are
expected to appear, before or after planting of the trees or plantations
at application rates between 0.25 kg and 5.0 kg, and preferably between
0.5 kg and 4.0 kg of active material per hectare.
The compounds of formula (I) may also be used to control the growth of
weeds, especially those indicated above, at loci which are not
crop-growing areas but in which the control of weeds is nevertheless
desirable.
Examples of such non-crop-growing areas include airfields, industrial
sites, railways, roadside verges, the verges of rivers, irrigation and
other waterways, scrublands and fallow or uncultivated land, in particular
where it is desired to control the growth of weeds in order to reduce fire
risks. When used for such purposes in which a total herbicidal effect is
frequently desired, the active compounds are normally applied at dosage
rates higher than those used in crop-growing areas as hereinbefore
described. The precise dosage will depend upon the nature of the
vegetation treated and the effect sought.
Pre- or post-emergence application, and preferably pre-emergence
application, in a directional or non-directional fashion (e.g. by
directional or non-directional spraying) at application rates between 1.0
kg and 20.0 kg, and preferably between 5.0 and 10.0 kg, of active material
per hectare are particularly suitable for this purpose.
When used to control the growth of weeds by pre-emergence application, the
compounds of formula (I) may be incorporated into the soil in which the
weeds are expected to emerge. It will be appreciated that when the
compounds of formula (I) are used to control the growth of weeds by
post-emergence application, i.e. by application to the aerial or exposed
portions of emerged weeds, the compounds of formula (I) will also normally
come into contact with the soil and may also then exercise a pre-emergence
control on later-germinating weeds in the soil.
Where especially prolonged weed control is required, the application of the
compounds of formula (I) may be repeated if required.
According to a further feature of the present invention, there are provided
herbicidal compositions comprising one or more of the isoxazole or
2-cyano-1,3-dione derivatives of formula (I) or agriculturally acceptable
salts or metal complexes thereof, in association with, and preferably
homogeneously dispersed in, one or more compatible
agriculturally-acceptable diluents or carriers and/or surface active
agents [i.e. diluents or carriers and/or surface active agents of the type
generally accepted in the art as being suitable for use in herbicidal
compositions and which are compatible with compounds of formula (I)]. The
term "homogeneously dispersed" is used to include compositions in which
the compounds of formula (I) are dissolved in other components. The term
"herbicidal compositions" is used in a broad sense to include not only
compositions which are ready for use as herbicides but also concentrates
which must be diluted before use. Preferably, the compositions contain
from 0.05 to 90% by weight of one or more compounds of formula (I).
The herbicidal compositions may contain both a diluent or carrier and
surface-active (e.g. wetting, dispersing, or emulsifying) agent.
Surface-active agents which may be present in herbicidal compositions of
the present invention may be of the ionic or non-ionic types, for example
sulphoricinoleates, quaternary ammonium derivatives, products based on
condensates of ethylene oxide with alkyl and polyaryl phenols, e.g. nonyl-
or octyl-phenols, or carboxylic acid esters of anhydrosorbitols which have
been rendered soluble by etherification of the free hydroxy groups by
condensation with ethylene oxide, alkali and alkaline earth metal salts of
sulphuric acid esters and sulphonic acids such as dinonyl- and
dioctyl-sodium sulphonosuccinates and alkali and alkaline earth metal
salts of high molecular weight sulphonic acid derivatives such as sodium
and calcium lignosulphonates and sodium and calcium alkylbenzene
sulphonates.
Suitably, the herbicidal compositions according to the present invention
may comprise up to 10% by weight, e.g. from 0.05% to 10% by weight, of
surface-active agent but, if desired, herbicidal compositions according to
the present invention may comprise higher proportions of surface-active
agent, for example up to 15% by weight in liquid emulsifiable suspension
concentrates and up to 25% by weight in liquid water soluble concentrates.
Examples of suitable solid diluents or carriers are aluminium silicate,
talc, calcined magnesia, kieselguhr, tricalcium phosphate, powdered cork,
absorbent carbon black and clays such as kaolin and bentonite. The solid
compositions (which may take the form of dusts, granules or wettable
powders) are preferably prepared by grinding the compounds of formula (I)
with solid diluents or by impregnating the solid diluents or carriers with
solutions of the compounds of formula (I) in volatile solvents,
evaporating the solvents and, if necessary, grinding the products so as to
obtain powders. Granular formulations may be prepared by absorbing the
compounds of formula (I) (dissolved in suitable solvents, which may, if
desired, be volatile) onto the solid diluents or carriers in granular form
and, if desired, evaporating the solvents, or by granulating compositions
in powder form obtained as described above. Solid herbicidal compositions,
particularly wettable powders and granules, may contain wetting or
dispersing agents (for example of the types described above), which may
also, when solid, serve as diluents or carriers.
Liquid compositions according to the invention may take the form of
aqueous, organic or aqueous-organic solutions, suspensions and emulsions
which may incorporate a surface-active agent. Suitable liquid diluents for
incorporation in the liquid compositions include water, glycols,
tetrahydrofurfuryl alcohol, acetophenone, cyclohexanone, isophorone,
toluene, xylene, mineral, animal and vegetable oils and light aromatic and
naphthenic fractions of petroleum (and mixtures of these diluents).
Surface-active agents, which may be present in the liquid compositions,
may be ionic or non- ionic (for example of the types described above) and
may, when liquid, also serve as diluents or carriers.
Powders, dispersible granules and liquid compositions in the form of
concentrates may be diluted with water or other suitable diluents, for
example mineral or vegetable oils, particularly in the case of liquid
concentrates in which the diluent or carrier is an oil, to give
compositions ready for use.
When desired, liquid compositions of the compound of formula (I) may be
used in the form of self-emulsifying concentrates containing the active
substances dissolved in the emulsifying agents or in solvents containing
emulsifying agents compatible with the active substances, the simple
addition of water to such concentrates producing compositions ready for
use.
Liquid concentrates in which the diluent or carrier is an oil may be used
without further dilution using the electrostatic spray technique.
Herbicidal compositions according to the present invention may also
contain, if desired, conventional adjuvants such as adhesives, protective
colloids, thickeners, penetrating agents, stabilisers, sequestering
agents, anti-caking agents, colouring agents and corrosion inhibitors.
These adjuvants may also serve as carriers or diluents.
Unless otherwise specified, the following percentages are by weight.
Preferred herbicidal compositions according to the present invention are:
aqueous suspension concentrates which comprise from 10 to 70% of one or
more compounds of formula (I), from 2 to 10% of surface-active agent, from
0.1 to 5% of thickener and from 15 to 87.9% of water;
wettable powders which comprise from 10 to 90% of one or more compounds of
formula (I), from 2 to 10% of surface-active agent and from 8 to 88% of
solid diluent or carrier;
water dispersible granules which comprise from 1 to 75%, e.g. 50 to 75%, of
one or more compounds of formula (I), from 2 to 10% of surface-active
agent and from 1 to 20%, e.g. 5-15%, of water soluble binder.
liquid emulsifiable suspension concentrates which comprise from 10 to 70%
of one or more compounds of formula (I), from 5 to 15% of surface-active
agent, from 0.1 to 5% of thickener and from 10 to 84.9% of organic
solvent;
granules which comprise from 1 to 90%, e.g. 2 to 10% of one or more
compounds of formula (I), from 0.5 to 7%, e.g. 0.5 to 2%, of
surface-active agent and from 3 to 98.5%, e.g. 88 to 97.5%, of granular
carrier and
emulsifiable concentrates which comprise 0.05 to 90%, and preferably from 1
to 60% of one or more compounds of formula (I), from 0.01 to 10%, and
preferably from 1 to 10%, of surface-active agent and from 9.99 to 99.94%,
and preferably from 39 to 98.99%, of organic solvent.
Herbicidal compositions according to the present invention may also
comprise the compounds of formula (I) in association with, and preferably
homogeneously dispersed in, one or more other pesticidally active
compounds and, if desired, one or more compatible pesticidally acceptable
diluents or carriers, surface-active agents and conventional adjuvants as
hereinbefore described. Examples of other pesticidally active compounds
which may be included in, or used in conjunction with, the herbicidal
compositions of the present invention include herbicides, for example to
increase the range of weed species controlled for example alachlor
[2-chloro-2,6'-diethyl-N-(methoxymethyl)-acetanilide], atrazine
[2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine], bromoxynil
[3,5-dibromo-4-hydroxybenzonitrile], chlortoluron
[N'-(3-chloro-4-methylphenyl)-N,N-dimethylurea], cyanazine
[2-chloro-4-(1-cyano-1-methylethylamino)-6-ethylamino-1,3,5-triazine],
2,4-D [2,4-dichlorophenoxy-acetic acid], dicamba
[3,6-dichloro-2-methoxybenzoic acid], acetochlor, difenzoquat
[1,2-dimethyl-3,5-diphenyl-pyrazolium salts], flampropmethyl [methyl
N-2--(N- benzoyl-3-chloro-4-fluoroanilino)-propionate], fluometuron
[N'-(3-trifluoro-methylphenyl)-N,N-dimethylurea], isoproturon
[N'-(4-isopropylphenyl)-N,N-dimethylurea], insecticides, e.g. synthetic
pyrethroids, e.g. permethrin and cypermethrin, and fungicides, e.g.
carbamates, e.g. methyl N-(1-butyl-carbamoyl-benzimidazol-2-yl)carbamate,
and triazoles e.g.
1-(4-chloro-phenoxy)-3,3-dimethyl-1-(1,2,4-triazol-1-yl)-butan-2-one.
Pesticidally active compounds and other biologically active materials which
may be included in, or used in conjunction with, the herbicidal
compositions of the present invention, for example those hereinbefore
mentioned, and which are acids, may, if desired, be utilized in the form
of conventional derivatives, for example alkali metal and amine salts and
esters.
According to a further feature of the present invention there is provided
an article of manufacture comprising at least one of the isoxazole or
2-cyano-1,3-dione derivatives of formula (I) or, as is preferred, a
herbicidal composition as hereinbefore described, and preferably a
herbicidal concentrate which must be diluted before use, comprising at
least one of the isoxazole or 2-cyano-1,3-dione derivatives of formula (I)
within a container for the aforesaid derivative or derivatives of formula
(I), or a said herbicidal composition, and instructions physically
associated with the aforesaid container setting out the manner in is which
the aforesaid derivative or derivatives of formula (I) or herbicidal
composition contained therein is to be used to control the growth of
weeds. The containers will normally be of the types conventionally used
for the storage of chemical substances which are solid at normal ambient
temperatures and herbicidal compositions -particularly in the form of
concentrates, for example cans and drums of metal, which may be internally
lacquered, and plastics materials, bottles or glass and plastics materials
and, when the contents of the container is a solid, for example granular,
herbicidal compositions, boxes, for example of cardboard, plastics
materials and metal, or sacks. The containers will normally be of
sufficient capacity to contain amounts of the derivatives of formula (I)
or herbicidal compositions sufficient to treat at least one acre of ground
to control the growth of weeds therein but will not exceed a size which is
convenient for conventional methods of handling. The instructions will be
physically associated with the container, for example by being printed
directly thereon or on a label or tag affixed thereto. The directions will
normally indicate that the contents of the container, after dilution if
necessary, are to be applied to control the growth of weeds at rates of
application between 0.01 kg and 20 kg of active material per hectare in
the manner and for the purposes hereinbefore described.
The following Examples illustrate herbicidal compositions according to the
present invention. The following are trade marks: Arylan; Synperonic;
Arkopon; Sopropon; Tixosil; Soprophor; Ethylan; Attagel; Rhodorsil.
EXAMPLE C1
An emulsifiable concentrate is formed from:
______________________________________
Active ingredient (Compound 1)
20% w/v
N-Methylpyrrolidone (NMP) 25% w/v
Calcium dodecylbenzenesulphonate 4% w/v
(CaDDBS) (Arylan CA)
Nonylphenol ethylene oxide propylene 6% w/v
oxide condensate
(NPEOPO) (Synperonic NPE 1800)
______________________________________
Aromatic solvent (Solvesso) to 100 volumes by stirring NMP, active
ingredient (Compound 1), CaDDBS, NPEOPO and 90% Aromatic solvent until a
clear solution is formed, and adjusting to volume with Aromatic solvent.
Similar emulsifiable concentrates may be prepared by replacing Compound 1
with other compounds of formula (Ia), (Ib) or (Ic).
EXAMPLE C2
______________________________________
Active ingredient (Compound 1)
50% w/w
Sodium dodecylbenzenesulphonate 3% w/w
(Arylan SX85)
Sodium methyl oleoyl taurate 5% w/w
(Arkopon T)
Sodium polycarboxylate 1% w/w
(Sopropon T36)
Microfine silicon dioxide 3% w/w
(Tixosil 38)
China clay 38% w/w
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by blending the above ingredients together and grinding the mixture in an
air jet mill.
Similar wettable powders may be prepared by replacing Compound 1 with other
compounds of formula (Ia), (Ib) or (Ic).
EXAMPLE C3
______________________________________
Active ingredient (Compound 1)
50% w/v
Antifreeze (Propylene glycol) 5% w/v
Ethoxylated tristyrylphenol 0.5% w/v
phosphate (Soprophor FL)
Nonyl phenol 9 mole ethoxylate 0.5% w/v
(Ethylan BCP)
Sodium polycarboxylate 0.2% w/v
(Sopropon T36)
Attaclay (Attagel) 1.5% w/v
Antifoam (Rhodorsil AF426R) 0.003% w/v
Water to 100 volumes
______________________________________
by stirring the above ingredients together and milling in a bead mill.
Similar suspension concentrates may be prepared by replacing Compound 1
with other compounds of formula (Ia), (Ib) or (Ic).
EXAMPLE C4
A water dispersible granule is formed from:
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Active ingredient (Compound 1)
50% w/w
Sodium dodecylbenzenesulphonate 3% w/w
(Arylan SX 85)
Sodium methyl oleoyl taurate 5% w/w
(Arkopon T)
Sodium polycarboxylate 1% w/w
Sopropon T36)
Binder (Sodium lignosulphonate) 8% w/w
China clay 30% w/w
Microfine silicon dioxide 3% w/w
(Tixosil 38)
______________________________________
by blending the above ingredients together, grinding the mixture in an air
jet mill and granulating by addition of water in a suitable granulation
plant (e.g. Fluid bed drier) and drying. Optionally the active ingredient
may be ground either on its own or admixed with some or all of the other
ingredients.
Similar water dispersible granules may be prepared by replacing Compound 1
with other compounds of formula (Ia), (Ib) or (Ic).
The compounds of the invention have been used in herbicidal applications
according to the following procedures.
METHOD OF USE OF HERBICIDAL COMPOUNDS
a) General
Appropriate quantities of the compounds used to treat the plants were
dissolved in acetone to give solutions equivalent to application rates of
up to 1000 g test compound per hectare (g/ha). These solutions were
applied from a standard laboratory herbicide sprayer delivering the
equivalent of 290 liters of spray fluid per hectare.
b) Weed control: Pre-emergence
The seeds were sown in 70 mm square, 75 mm deep plastic pots in non-sterile
soil. The quantities of seed per pot were as follows:
______________________________________
Approx number of seeds/pot
______________________________________
Weed species
1) Broad-leafed weeds
Abutilon theophrasti 10
Amaranthus retroflexus 20
Galium aparine 10
Ipomoea purpurea 10
Sinapis arvensis 15
Xanthium strumarium 2
2) Grass weeds
Alopecurus myosuroides 15
Avena fatua 10
Echinochloa crus-galli 15
Setaria viridis 20
3) Sedges
Cyperus esculentus 3
Crop
1) Broad-leafed
Cotton 3
Soya 3
2) Grass
Maize 2
Rice 6
Wheat 6
______________________________________
The compounds of the invention were applied to the soil surface, containing
the seeds, as described in (a). A single pot of each crop and each weed
was allocated to each treatment, with unsprayed controls and controls
sprayed with acetone alone.
After treatment the pots were placed on capillary matting kept in a glass
house, and watered overhead. Visual assessment of crop damage was made
20-24 days after spraying. The results were expressed as the percentage
reduction in growth or damage to the crop or weeds, in comparison with the
plants in the control pots.
c) Weed control: Post-emergence
The weeds and crops were sown directly into John Innes potting compost in
75 mm deep, 70 mm square pots except for Amaranthus which was pricked out
at the seedling stage and transferred to the pots one week before
spraying. The plants were then grown in the greenhouse until ready for
spraying with the compounds used to treat the plants. The number of plants
per pot were as follows:
______________________________________
No. of plants
per pot Growth stage
______________________________________
1) Broad leafed weeds
Weed species
Abutilon theophrasti 3 1-2 leaves
Amaranthus retroflexus 4 1-2 leaves
Galium aparine 3 1.sup.st whorl
Ipomoea purpurea 3 1-2 leaves
Sinapis arvensis 4 2 leaves
Xanthium strumarium 1 2-3 leaves
2) Grass weeds
Weed species
Alopecurus myosuroides 8-12 1-2 leaves
Avena fatua 12-18 1-2 leaves
Echinochloa crus-galli 4 2-3 leaves
Setaria viridis 15-25 1-2 leaves
3) Sedges
Weed species
Cyperus esculentus 3 3 leaves
1) Broad leafed
Crops
Cotton 2 1 leaf
Soya 2 2 leaves
2) Grass
Crops
Maize 2 2-3 leaves
Rice 4 2-3 leaves
Wheat 5 2-3 leaves
______________________________________
The compounds used to treat the plants were applied to the plants as
described in (a). A single pot of each crop and weed species was allocated
to each treatment, with unsprayed controls and controls sprayed with
acetone alone.
After treatment the pots were placed on capillary matting in a glass house,
and watered overhead once after 24 hours and then by controlled
sub-irrigation. Visual assessment of crop damage and weed control was made
20-24 days after spraying. The results were expressed as the percentage
reduction in growth or damage to the crop or weeds, in comparison with the
plants in the control pots.
When applied post-emergence at 1000 g/ha or less compounds 1-7 and 110-115
gave at least 90% reduction in growth of one or more of the weed species.
When applied pre-emergence at 1000 g/ha or less compounds 1-7 and 110-115
gave at least 70% reduction in growth of one or more of the weed species.
At levels of application toxic to the weeds these compounds were selective
in at least one of the crop species.
While the invention has been described in terms of various preferred
embodiments, the person skilled in the art will appreciate that various
modifications, substitutions, omissions and changes can be made without
departing from the spirit thereof. Accordingly, it is intended that the
scope of the present invention be limited solely by the scope of the
following claims, including equivalents thereof.
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